Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

8-hydroxyguanine(oh8Gua), a premutagenic DNA adduct formed by active oxygens, has been suggested to be relevant to aging. oh8Gua glycosylase (ogg1) removes oh8Gua residues from DNA and prevents the mutation. In the present study, we compared the oh8Gua contents and oh8Gua glycosylase activities in various organs at 2, 8, 14 months of age between senescence-prone strain (SAMP1 and SAMP8) and senescence-resistant strain (SAMR1) of senescence-accelerated mice (SAM; a murine model of accelerated aging). In all the organs of SAMP1 and SAMP8 mice at all ages examined, oh8Gua glycosylase activity was markedly reduced to approximately 10 - 40% of corresponding senescence-resistant SAMR1 mice and oh8Gua content in DNA was much increased. RNA blot analysis revealed no reduction in mRNA levels of ogg1 gene in SAMP mice. We identified a novel R304W point mutation in the mogg1 gene in SAMP mice, which may be responsible for the reduced activity. We propose that the impairment of oh8Gua repair in SAMP mice may be one of the factors contributing to accelerated senescence.

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Presentation Number SAchung0735
Keywords: aging, 8-hydroxyguanine, ogg1, SAMP mice, repair